The Journal of Arthroscopy and Related Surgery

2019 Arthroscopy Techniques

Musculoskeletal (MSK) disorders are one of the leading causes of physical disability worldwide, and the treatment and prevention of MSK disorders can alleviate substantial indirect and direct health care costs.1 Leukocyte-rich platelet-rich plasma (LR-PRP) has been used to treat the injured MSK system by initiating the healing and regeneration processes. LR-PRP is composed of elevated numbers of leukocytes and platelets that infiltrate the site of injury where inflammatory factors (i.e., tumor necrosis factor α [TNF-α], interleukin [IL] 1β, IL-6, and IL-8) and angiogenic factors (i.e., vascular endothelial growth factor [VEGF], platelet-derived growth factor [PDGF], and insulin growth factor [IGF]) are released into the extracellular space. Growth factors and other cytokines in platelet concentrates have shown a temporal effect on various MSK conditions but are highly variable in concentration depending on the preparation methodology and donor demographic characteristics. Age and sex contribute to the biological variances of cytokines and chemokines in platelet-rich plasma (PRP) and may have a significant role in tissue healing responses and outcomes. Evanson found that female persons had elevated concentrations of endothelial growth factor, hepatocyte growth factor, IGF, and PDGF-BB compared with male persons and that levels of endothelial growth factor, IGF-1, PDGF-AB, PDGF-BB, and transforming growth factor β1 were significantly higher in young donors. Studies reporting on significant associations between growth factors and age or sex might also indicate that biological variability exists not only among individual donors but also as a result of variation in specific preparation processes.

Many patients with MSK pain often choose pharmaceutical agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), as the first line of treatment to alleviate pain and reduce inflammation. However, NSAIDs can deter platelet function and potentially obviate growth factor levels and cytokine signaling. The mechanism of action of NSAIDs is to inhibit platelet activation by irreversibly binding to cyclooxygenase (COX) enzymes and to influence the arachidonic acid pathway.13, 14 Enzyme inhibition can cause platelet dysfunction through the platelets’ 7- to 10-day life span. Nonselective NSAIDs, such as naproxen, alter platelet function by prolonging bleeding time, slowing platelet aggregation and activation, and reducing thromboxane levels. NSAIDs are known to impair function of platelets and biological constituents in whole blood by selectively inhibiting cytokine production,19 such as PDGF20; fibroblast growth factor 2 (FGF-2); VEGF; IL-1β, IL-6, and IL-8; and enhancing TNF-α. However, limited data exist regarding the molecular influence of NSAIDs on PRP. In addition, there is little evidence to guide physicians as to when it is beneficial to harvest and administer PRP therapy in patients who use NSAIDs.

A 1-week washout period was chosen because this is typically the amount of time we ask our surgical patients to refrain from NSAID use before surgical intervention. Suggested washout periods are not directly related to the NSAIDs’ half-life (3-4 days) but are recommended to allow targeted prostaglandins to replenish at the tissue level, therefore preventing long-term inhibition of COX-1 isoenzymes. The simplest model to observe the effect of naproxen on angiogenic and proinflammatory factors in LR-PRP was to evaluate normative values of biological factors in healthy donors.

The purpose of this study was to quantify and compare normative catabolic and anabolic factor concentrations in LR-PRP at various time points, including baseline, 1 week after initiating naproxen use, and after a 1-week washout period. Our primary hypothesis was that naproxen use would alter both the catabolic and anabolic biological factors in LR-PRP. Our secondary hypothesis was that discontinuing naproxen use for 1 week would be sufficient to return LR-PRP’s biological constituents to baseline.

Full Article: The Influence of Naproxen on Biological Factors in Leukocyte-Rich Platelet-Rich Plasma: A Prospective Comparative Study

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